Fluid control is necessary for many systems capable of automated chemical and biochemical analysis. These systems typically require liquid samples, reagents, and buffers to be dispensed in a controlled manner. Making these analysis systems portable presents unique demands on fluidics systems that have not been successfully met by currently available technology. These demands stem from the combined requirements of automation, compact size and compatibility with unprocessed samples, especially for field operations or point-of-care applications.
For laboratory-scale devices, there is an assortment of mechanical valves suitable for fluid handling and control. However, the size of these components makes them impractical for portable analysis systems. While small valves of analogous design have been developed and are commercially available, as the valve size is reduced, clogs by the components of complex sample matrices become an important limitation.
Micro-total analysis systems (F-TAS) perform integrated chemical analysis and fluid control on the micron scale. Many of these systems are capable of valveless fluid control by means of electrokinetic pumping and switch-driving pressures. (Manz, A. et al. in Micro Total Analysis Systems; and van den Berg, A. et al., Academic Publishers, Dordrecht, 1995, pp. 5-27). However, micron-scale channels can become clogged when unprocessed environmental and clinical samples are used. In addition, materials can be adsorbed onto channel walls and interfere with osmotic pumping. Furthermore, these devices have a relatively low-volume throughput making them impractical for the analysis of milliliter volumes, as may be required for accurate measurement of trace constituents or analysis of inhomogeneous samples.
The need for intermediate scale fluid handling systems has been identified. (VerLee, D. et al., Technical Digest, Solid-State Sensor and Actuator Workshop, 1996, pp. 9-14) Among the developments in this area are pneumatic diaphragm valves integrated directly into the device's fluidics channels. This approach provides fluid regulation while adding only slightly to the overall size of the system. However, diaphragm-based valves can suffer from sticking, clogging, and performance loss due to diaphragm aging.
Valveless fluid control has also been developed, thus eliminating the problem of valve clogging by suspended contaminants. For example, pressure control and pressure differentials can switch fluid flow between micro-channels. (Brody, J. P., 1998, U.S. Pat. No. 5,726,404) This method of fluid control is based on the application and regulation of differential pressures to each fluid channel and is only applicable in the low Reynolds number regime. The regulation of differential pressures makes the design inherently complex and, further, the requirement for pressure sources and regulators limits the feasibility of this method for portable instrumentation. The limitation with regard to the low Reynolds numbers regime makes the method impractical for the control of aqueous fluids in channels greater than approximately 100 microns. (Brody, J. P. et al., Technical Digest, Solid-State Sensor and Actuator Workshop, 1996, pp. 105-108; and Brody, J. P., Biophysical Journal, 1996, 71, pp. 3430-3441). Although valves may not be clogged with these approaches, the fluid channels themselves are likely to be clogged by suspended contaminants. Electrokinetic pumping and switching systems have also accomplished valveless fluid control in micron-scale devices. (Manz et al., Advances in Chromatography, 1993, 33, pp. 1-67.) Similarly, however, these designs are limited to the low Reynolds number regime, where micron-scale channels are prone to clogging. Further, these methods require large driving potentials, typically on the order of a kilovolt, and fluid flow that can be drastically affected by sample components adhering to the wall of the channel.